Prototek has developed some very select inhibitors to a the cysteine protease class of enzymes and these inhibitors have been demonstrated to be effective inhibitors of a number of pathogens. From its arsenal of over eighty of these inhibitors, two of thes have shown exciting efficacy against Pneumocystis carinii in culture and in in vivo mouse models of the disease. Therefore, our hypothesis is that an essential cysteine protease is a practical target for chemotherapy. Success will be achieved by the following objectives: a) synthesize two tritium labeled inhibitors whose unlabeled counterparts have been shown to be efficacious in models of pneumocystis carinii pneumonia. b) determine the fate of the inhibited enzyme in vivo in mice and in cultured parasites c) evaluate inhibitors for oral availibility and tissue selectivity d) determine the physiological distribution of the inhibition e) create a data base of efficacy vs structure of the design of future inhibitors f) using standard cell biology techniques as well as internal specialized techniques begin to characterize the labeled enzymes. PROPOSED COMMERCIAL APPLICATION This SBIR project focuses on the synthetic technology designed to make inhibitors that are not only specific to the class of cysteine proteases associated with Pneumocytsis carinii but also specific to particular individual enzymes of the class and safe enough to be used in humans. Now pneumocystis carinii pneumonia is the leading cause of death in AIDS patients. The prototek approach develops novel chemotherapeutics that act by different mechanisms than the current therapies. This promises to be an important advancement of medicine.